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Associations between 2 paternal casein haplotypes and milk yield traits of Swiss Fleckvieh cattle. Martin H. Braunschweig. Institute of Genetics, Vetsuisse ...
J Appl Genet 49(1), 2008, pp. 69–74

Original article

Associations between 2 paternal casein haplotypes and milk yield traits of Swiss Fleckvieh cattle Martin H. Braunschweig Institute of Genetics, Vetsuisse Faculty, University of Berne, Berne, Switzerland

Abstract. Associations between casein haplotypes and milk yield traits of offspring from 5 Swiss Fleckvieh AI test bulls were investigated. The analysis was performed by using a daughter design, where each daughter inherited either paternal haplotype B-A1-A-A or B-A2-A-A for alleles of as1-, b-, as2- and k-casein genes. The substitution effects of paternal CSN2 A1 versus A2 on protein yield deviations (YDs) were significant (P < 0.05), whereas their effects on milk and fat YDs were not. The paternal substitution effects of the CSN2 A1 versus the A2 allele on protein YDs within the 5 sires did not reach the significance level. This is due to the contrary allele substitution effect of a sire compared to the other 4 sires. The effects of maternal haplotypes on milk, protein and fat YDs were not significant. However, it is noteworthy that the effects of haplotypes with a low frequency in the population deviate largely from the most frequent haplotype B-A2-A-A. The effects of b-lactoglobulin (BLG) genotypes were significant for protein YDs but not for milk and fat YDs. The association between the paternal CSN2 A1 and A2 alleles and milk protein YDs within sires but not milk and fat YDs indicate an interaction, which might be a consequence of CSN2 heterogeneity or a closely linked gene that is contributing to the estimated effects. Keywords: casein haplotype, daughter design, genetic variant, milk yield trait, Swiss Fleckvieh cattle.

Introduction The 4 bovine caseins (CNs) as1-, as2-, b- and k-CN (corresponding genes: CSN1S1, CSN1S2, CSN2 and CSN3, respectively) constitute about 80% of the protein content of milk and are associated with the casein micelle. The remaining about 20% of milk protein content consists of whey proteins, with b-lactoglobulin (b-LG, gene BLG) being the main fraction. The 4 casein genes were mapped to bovine chromosome 6 (BTA6) at q31-33 by in situ hybridisation (Threadgill and Womack 1990). The order was found to be CSN1S1-CSN2CSN1S2-CSN3, residing on about 200–300 kb of DNA (Ferretti et al. 1990; Threadgill and Womack 1990). This order was recently confirmed and the 4 casein genes were assembled in the third release of the draft bovine genome sequence from BTA6 within approximately 250 kb (bovine genome sequence version Btau_3.1).

Since the discovery of genetic polymorphism of milk proteins by Aschaffenburg and Drewry (1955), a large number of studies have focused on the relationship between milk protein loci and milk composition and yield traits in cattle (Aleandri et al. 1990; Bovenhuis et al. 1992). Bovenhuis et al. (1992) suggested that associations between casein alleles and milk production traits are due to the effect of linked loci rather than caused by the milk protein loci themselves. The finding of an association between the casein loci and BTA6 QTL effects on milk production traits would then depend on these linked genes. Consequently, effects should be studied within families. Because of the tight genetic linkage of the casein loci, Grosclaude (1988) recommended to study casein haplotypes rather than single alleles. This approach makes it possible to account for interactions between the casein loci on the same chromosome.

Received: June 6, 2007. Revised: August 22, 2007. Accepted: October 9, 2007. Correspondence: M. Braunschweig, Institute of Genetics, Vetsuisse Faculty, University of Berne, CH–3001 Berne, Switzerland; e-mail: [email protected]

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A recent review has shown that, in various cattle breeds, BTA6 harbours the most significant QTL for milk production, as compared to the other bovine chromosomes (Khatkar et al. 2004). The outstanding results of these QTL studies are 2 proposed functional mutations in a 450-kb region underlying QTLs for milk production traits (Cohen-Zinder et al. 2005; Schnabel et al. 2005). In several association studies the effects of casein haplotypes on milk production traits were estimated (Lien et al. 1995; Braunschweig et al. 2000; Ikonen et al. 2001; Boettcher et al. 2004). Other groups reported the presence of QTLs for milk production traits linked to the casein gene cluster (Velmala et al. 1999; Schnabel et al. 2005). Due to these findings, the casein haplotypes are still among the candidates in the attempt to identify alleles, which affect milk production traits. In Switzerland the introduction of Red Holstein genes into the Simmental population began in 1968. These crosses are referred to as Swiss Fleckvieh and form a section apart from Simmental and Red Holstein. The objective of this study was to estimate substitution effects of 2 casein haplotypes within groups of paternal half-sibs (daughters of 5 Swiss Fleckvieh AI test bulls) on milk, protein and fat yield. The casein haplotypes differed at the CSN2 locus and thus paternal allele substitution effects of allele A1 versus allele A2 were estimated.

B-A1-A-A and B-A2-A-A for alleles of CSN1S1, CSN2, CSN1S2 and CSN3, were found and selected to estimate their CSN2 substitution effects on milk yield traits. The chromosome sections were marked by alleles A1 and A2, which are the most frequent CSN2 alleles in Swiss Fleckvieh. The bulls were tested exclusively on first-lactation cows, and for their progeny testing, inseminations were balanced over geographical regions and time. It was assumed that dams were a random sample from the Swiss Fleckvieh population with respect to their casein genotype, polygenic merits and percentage of Red Holstein genes and evenly distributed between the 2 paternal haplotype groups. In Table 1 the 5 selected sires with their percentage of Red Holstein genes and the number of the daughters grouped according to the inherited paternal haplotype are given.

Materials and methods

The milk protein variants of caseins and b-LG were phenotyped by means of isoelectric focusing (IEF) (Seibert et al. 1985). Daughters with the very rare allele CSN3 E in the Swiss Fleckvieh population were excluded from the study. The daughters whose paternal haplotype could not be unambiguously inferred from their parents, were excluded from the investigation. In Table 2 the number of daughters grouped according to parental casein haplotypes and daughter BLG genotypes are presented. The assignment of paternal haplotypes to daughters heterozygous A1A2 for CSN2 was limited by non-informative heterozygous CSN2 A1A2 dams. In addition a limited number of dams were available to phenotype for the milk protein variants. The groups with maternal haplotypes B-A2-A-A and B-A2-A-B in combination with paternal haplotype B-A1-A-A are therefore small compared with the corresponding combination with paternal haplotype B-A2-A-A. The same applies to maternal haplotypes with CSN2 A1 in combination with paternal haplotype

The estimation of an allele substitution effect on a quantitative trait within half-sibs requires sires in the heterozygous state for the gene of interest. The daughter design proposed by Geldermann et al. (1985) was used for this investigation. Because most genes influencing a quantitative trait are not known, the investigation has to include several families to estimate effects of marked chromosome sections (Geldermann et al. 1985). From a random sample of frozen semen of the 18 Swiss Fleckvieh test bulls, DNA was isolated according to the modified protocols described by Lien et al. (1990). Genotyping of bulls for CSN1S1, CSN2, CSN1S2, CSN3 and BLG genes was performed by allele-specific polymerase chain reaction (ASPCR) and polymerase chain reaction with subsequent restriction fragment length polymorphism (PCR/RFLP) (Schlieben et al. 1991; Schlee et al. 1992). Five of these 18 genotyped test bulls, each carrying the haplotypes

Table 1. Number of daughters grouped according to inherited paternal casein haplotype Sire (Red Holstein genes in %)

Gregor (68) Tarocco (75) Dustin-ET (93) Koloman (88) Morello (94) Total

Number of daughters with paternal CSN1S1, CSN2, CSN1S2 and CSN3 alleles B-A1-A-A 34 25 25 28 28 140

B-A2-A-A 23 47 30 28 18 146

Casein haplotypes and milk yield traits Table 2. Number of daughters grouped according to inherited parental casein haplotypes and the BLG genotype Haplotype or genotype

Number of daughters with paternal CSN1S1, CSN2, CSN1S2 and CSN3 alleles B-A1-A-A

B-A2-A-A

Maternal CSN1S1, CSN2, CSN1S, and CSN3 alleles B-A1-A-A 67 15 B-A2-A-A 7 74 B-A1-A-B 43 13 B-A2-A -B 3 24 B-B-A-A 12 9 B-C-A-B 8 11 Total 140 (49%) 146 (51%) BLG genotype of daughters AA 14 22 AB 76 72 BB 50 52

B-A2-A-A. However, it is assumed that the successful assignment of the daughters’ haplotypes is random and similar within the sires. The yield deviations (YDs) of milk yield traits were calculated from lactation records by adjusting for all environmental effects taken into account in the estimation of breeding values and also for half of the breeding value of the dam (VanRaden and Wiggans 1991, Swiss Fleckvieh Breeder’s Federation). The Swiss Fleckvieh Breeder’s Federation kindly provided for all genotyped cows the YDs for milk, protein and fat yields. The associations between the YDs of milk production traits and the casein haplotypes as well as BLG genotypes were evaluated by using the mixed procedure of SAS (version 6.12). Variance components were estimated with REML. The model selection was based on the Akaike information criterion (AIC). Furthermore, I tested whether there are significant interactions between the parental haplotypes as well as the BLG genotype. The percentage of Red Holstein genes was included in the model selection process as a covariate to estimate its contribution and its impact on the variance explained by the parental haplotypes or the BLG genotype. The F-test that compares the variance explained by the factors included in the model with the total variance was also considered to select the model. The paternal and the maternal haplotype as well as the BLG genotype were the variables of interest and forced to remain in the model. The final model was: yijklm= m + si + hpsj + hpdk + blgl + eijklm , where yijklm = observation of daughter ijklm from sire i, with sire haplotype j, dam haplotype k and

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BLG genotype l; m = overall mean; si = random effect of sire i; hpsj = fixed effect of haplotype j inherited from the sire; hpdk = fixed effect of the haplotype k inherited from the dam; blgl = fixed effect of genotype l of BLG; and eijklm = random residual effect of observation ijklm. For paternal haplotypes nested within sire, the same model was used but instead of the fixed effect hpsj, a random effect hpsj(i) was included in the model. This corresponds to the interaction between the random sire effect and its haplotypes.

Results No interactions between parental haplotypes and the BLG genotype turned out significant. Including the percentage of Red Holstein genes in the model did not change the effects of the haplotypes and the BLG genotypes, so this factor was excluded from the models. The estimated effects on YDs of milk yield traits are given in Table 3. The effects of paternal casein haplotypes on protein YDs were significant, whereas no associations were found between these haplotypes and YDs in kg milk and fat. The maternal haplotypes were not significantly associated with YDs in milk yield traits. However, it is worthwhile to mention that the effects of haplotypes with a low frequency in the population deviate largely from the most frequent haplotype B-A2-A-A. The BLG genotypes had significant effects on YDs in kg protein, with BLG AA cows producing more protein. The effects of paternal haplotypes within sire on YDs in kg milk, kg protein and kg fat were estimated in order to verify whether there are significant interactions between the sire effect and its haplotypes. No significant associations were found for these interactions. However, a barely indicative interaction (P = 0.112) was observed for YDs in kg protein, suggesting that not all the effects of haplotype B-A2-A-A are superior over those of haplotype B-A1-A-A within all 5 sires. In Table 4 the estimates for the paternal haplotypes within sires are presented. The effect of haplotype B-A2-A-A is set to 0. Interestingly, the estimated effect of haplotype B-A1-A-A of sire Koloman shows a slight superiority over the effect of B-A2-A-A, pointing towards allelic heterogeneity across families for the casein complex and/or its neighbouring genes, respectively. To test the contribution of the sire Koloman to the analysis, the data have been reanalysed, excluding the observations for the offspring of sire Koloman. The paternal haplotype became significant on YDs in kg

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Table 3. Estimates (Est.) and standard errors (SE) of yield deviations (YDs) of milk yield traits for casein haplotypes and BLG genotypes Milk YD (kg)

Haplotype or genotype Est.

Protein YD (kg) SE

Est.

Paternal CSN1S1, CSN2, CSN1S, and CSN3 alleles1 B-A1-A-A –123.5 83.0 P 0.138 Maternal CSN1S1, CSN2, CSN1S, and CSN3 alleles2 B-C-A-B –295.6 136.4 B-B-A-A –191.6 133.8 B-A2-A-B 34.9 116.7 B-A1-A- B –84.3 107.8 B-A1-A-A –36.1 101.6 P 0.221 BLG genotype of daughters3 AA 122.9 118.6 AB –45.3 84.4 P 0.230 1 3

Fat YD (kg)

SE

Est.

SE

–5.7